In orthodontics, timing of growth modification in adolescents is an important determinant of treatment success. Treatment results depend on the rates of bone growth which vary during different stages of maturation. However, currently no reliable markers exist for measuring changes in bone growth stages. The purpose of this study is to explore the use of specific urinary metabolites of bone collagen as markers for timing of orthodontic treatment. The specific aims are 1) to correlate urinary hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) excretion with facial bone growth velocity, 2) to provide a diagnostic decision rule to determine an individual's adolescent maturational stage, and 3) to evaluate the outcome of facial orthopaedic treatment as a function of the HP and LP excretion at the start of treatment. A prospective cohort study is designed in which urine samples, facial and statural growth measurements are gathered from adolescents on a monthly basis. From these data, the correlation between facial growth velocity and urinary HP/creatinine and LP/creatinine excretion ratios will be investigated using generalized estimating equations. Different adolescent maturational stages will be derived from the statural height growth velocity curves which will be smoothed using a cubic spline method. A diagnostic decision rule will be constructed using logistic discriminant analysis to classify individuals in maturational stages using HP and LP excretion, age and sex. A subgroup of the cohort will be comprised of patients that are treated with mandibular orthopaedic appliance. The results of treatment will be evaluated as a function of the quantity of urinary excretion of HP and LP at the start of treatment. The potential clinical implication is that the proposed urinary markers would allow orthodontists to time growth intervention to obtain optimum treatment results.